Scherzer (13-7) allowed just one run on five hits and a walk. He fanned six and a established a new career-high for wins in a season.
Alex Avila and Jhonny Peralta hit back-to-back home runs for the Tigers, who hold a 2 1/2 lead over the Indians for first place in the AL Central.
Jose Valverde tossed a 1-2-3 ninth to record his 36th save of the season.
Josh Tomlin (12-6) lasted 6 2/3 innings, allowing four runs on six hits. He struck out two and did not issue a walk.
Carlos Santana scored the lone run for the Indians, who had won two straight entering the series.
Tomlin was dominant through five frames. He surrendered just two hits and did not allow a runner to advance past first base over that span. In the sixth, however, Ryan Raburn reached with a one-out single and Jackson belted an 0-1 sinker over the fence in left-center to put the Tigers on top.
Santana began the next frame with a single. Scherzer retired the next two batters, then threw a 2-2, knee-high fastball by Lonnie Chisenhall, but home plate umpire Joe West called the pitch a ball. Chisenhall capitalized, ripping a grounder towards first. Miguel Cabrera made a diving stop, but his toss pulled the covering Scherzer off the bag, allowing runners to reach the corners. Santana came home one batter later on a wild pitch to make it 2-1.
With two down in the bottom half, Avila jumped on the first offering from Tomlin and sent it over the fence in right. Peralta repeated the feat, sending the first pitch he saw into the stands in left, marking the end of Tomlin's outing.
"I was happy the way I threw the ball for five innings," said Tomlin. "After that you have to make better pitches in certain situations."
Joaquin Benoit and Valverde teamed up to keep the margin at three, closing out the game with two scoreless relief innings.
Cleveland had its chances against Scherzer early on. Shin-Soo Choo worked a one-out walk in the first, advanced to second on a wild pitch and to third on an Asdrubal Cabrera groundout, but was stranded when Travis Hafner went down on strikes.
Michael Brantley ripped a two-out double in the third, but Choo followed with a groundout.
In the sixth, Choo singled and stole second with two down, but again Hafner was retired to end the threat.
"At this point in the season, when you can play a team in second place and beat them, that's always huge," said Scherzer. "That's what it's going to take for us to make the playoffs. We had a good team win tonight."
Tomlin has allowed a team-high 23 home runs this season...Miguel Cabrera went 1-for-4, extending his hit streak to 16-games...On Friday, the Indians placed rookie second baseman Jason Kipnis on the 15-day disabled list with a strained right hamstring, optioned outfielder Ezequiel Carrera to Triple-A Columbus and recalled outfielder Shelley Duncan and infielder Luis Valbuena from Columbus...Also on Friday, the Indians announced the August 14 postponed game against the Twins has been rescheduled for a doubleheader on Saturday, September 24.